WO 2005/080316 (in the name of University College London) discloses compounds capable of modulating cannabinoid or cannabinoid-like receptors, including VSN16, the structure of which is shown below.

Initial studies demonstrated that VSN16 and related compounds exhibited a marked effect on spasticity in CREAE mice, providing strong evidence that a selective inhibition of spasticity was achieved without producing significant adverse CNS effects. Studies also demonstrated that the compounds inhibited gastrointestinal motility, as measured using a colonic propulsion test. VSN16 is understood to act on the endothelium to release nitric oxide and activate KCa and TRPV1. Its solubility is believed to play a significant role in bringing about peripheral cannabinoid-like effects without accompanying central or severe cardiovascular responses.
WO 2005/080316 discloses the preparation of VSN16 as shown in Scheme 1 below.

A palladium catalysed Songashira coupling reaction was used to insert a variety of alkyl side chains into 3-iodo methyl benzoate. The target compounds (S5) and related analogues were synthesised by a simple four-step route. First, the acid (S1) was reacted with DL alaninol in the presence of a diimide (EDCI) to give the amide (S2) in good yield. Palladium-catalysed coupling [Hoye, R. C. et al, J. Org. Chem. 1999, 64, 2450-2453; Hopper, A. T. et al, J. Med. Chem. 1998, 41, 420-427] of the amide with the alkyne acid in the presence of CuII and pyrrolidine proceeded smoothly to give the alkyne (S3). The acid (S3) was quantitatively transformed into (S4) using ethylchloroformate and dimethylamine HCl. Lindlar catalysed reduction yielded the target alkene (S5). Alternatively, (S4) can be reduced with borohydride (polymer supported), (CH3COO)2Ni.4H2O, MeOH, and H2 at atmospheric pressure (P. M. Hoi, C. Visintin, M. Okuyama, S. M. Gardiner, T. Bennett, D. Baker, D. L. Selwood and C. R. Hiley; British Journal of Pharmacology, 2007, 1-14). The flexibility of this method allows the synthesis of a large number of different compounds using a range of alkynes for the Sonogashira coupling, or by starting with a different amine for the amide formation in the first step. However, the main drawback of this synthetic route is that the Lindlar catalytic reduction of intermediate (S4) yields a mixture of E- and Z-isomers of the resulting alkenyl compounds, requiring separation by reverse phase HPLC. This technique is both costly and time consuming, thereby rendering the method unsuitable for large scale synthesis.
More recently, WO 2010/116116 (UCL Business PLC) disclosed an alternative process for preparing VSN16 and related compounds. Specifically, WO 2010/116116 disclosed the preparation of VSN16 by the process set forth in Scheme 2 below, which comprises the steps of:                treating a compound of formula IV.1 with a compound of formula V.1 to form a compound of formula IIIb.1;        treating said compound of formula IIIb.1 with a compound of formula IIb.1, where PG is a protecting group, to form a compound of formula Ib.1; and        removing protecting group PG from said compound of formula Ib.1 to form VSN16        

Advantageously, compound IIIb.1 can be separated from the corresponding Z isomer by crystallisation. This avoids the need for costly and time consuming purification using reverse phase HPLC, as required by previously described processes for preparing VSN16 and analogues thereof. Moreover, the ability to separate the E- and Z-isomers by crystallisation renders the process suitable for scale-up and contributes to an improved overall yield.
VSN16 prepared in accordance with the prior art methods described above is in the form of an oil. Ideally, for large scale preparation and purification purposes, it would be advantageous if VSN16 could be processed as a solid.
Accordingly, the present invention seeks to provide the compound VSN16 in crystalline form. In particular, the invention seeks to provide crystalline forms that retain the desired pharmacological activity of the compound. More specifically, but not exclusively, the present invention seeks to provide crystalline forms of the compound VSN16 that exhibit one or more improved properties.